An isomorphous replacement method for efficient de novo phasing for serial femtosecond crystallography

Keitaro Yamashita, Dongqing Pan, Tomohiko Okuda, Michihiro Sugahara, Atsushi Kodan, Tomohiro Yamaguchi, Tomohiro Murai, Keiko Gomi, Naoki Kajiyama, Eiichi Mizohata, Mamoru Suzuki, Eriko Nango, Kensuke Tono, Yasumasa Joti, Takashi Kameshima, Jaehyun Park, Changyong Song, Takaki Hatsui, Makina Yabashi, So IwataHiroaki Kato, Hideo Ago, Masaki Yamamoto, Toru Nakatsu

Research output: Contribution to journalArticlepeer-review

51 Citations (Scopus)

Abstract

Serial femtosecond crystallography (SFX) with X-ray free electron lasers (XFELs) holds great potential for structure determination of challenging proteins that are not amenable to producing large well diffracting crystals. Efficient de novo phasing methods are highly demanding and as such most SFX structures have been determined by molecular replacement methods. Here we employed single isomorphous replacement with anomalous scattering (SIRAS) for phasing and demonstrate successful application to SFX de novo phasing. Only about 20,000 patterns in total were needed for SIRAS phasing while single wavelength anomalous dispersion (SAD) phasing was unsuccessful with more than 80,000 patterns of derivative crystals. We employed high energy X-rays from SACLA (12.6 keV) to take advantage of the large anomalous enhancement near the L III absorption edge of Hg, which is one of the most widely used heavy atoms for phasing in conventional protein crystallography. Hard XFEL is of benefit for de novo phasing in the use of routinely used heavy atoms and high resolution data collection.

Original languageEnglish
Article number14017
JournalScientific reports
Volume5
DOIs
Publication statusPublished - 2015 Sept 11
Externally publishedYes

ASJC Scopus subject areas

  • General

Fingerprint

Dive into the research topics of 'An isomorphous replacement method for efficient de novo phasing for serial femtosecond crystallography'. Together they form a unique fingerprint.

Cite this